THE  PREPARATION  OF  GAMMA-DIPROPYLAMI- 
NOETHYLESTER  OF  PARA-ANI 
NOBENZOIC  ACID 


BY 

WALTER  EMERSON  BAUS 


THESIS 


For  the  Degree  of  Bachelor  of  Science 


IN 


CHEMISTRY 


COLLEGE  OF  LIBERAL  ARTS  AND  SCIENCES 
UNIVERSITY  OF  ILLINOIS 


1921 


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ACKNOWLEDGEMENT 
The  writer  wishes,  at  this 

time,  T,o  express  his  appreciation 

for  the  invaluable  assistance  of 

Professor  Roger  Adams,  who  suggested 

ohe  problem  and  under  whose  able 

direction  this  research  was  done. 


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TABLE  OP  CONTENTS 


PART  1 

I  INTRODUCTION 

II  HISTORICAL  AND  THEORETICAL 

III  EXPERIMENTAL 

a Propyl  bromide 
b Para-Toluenesulfonamide 
c Para-Toluenesulfondipropylamlde 
d Dlpropylamlne 
e Ethylene  oxide 
f Dipropylaminoethyl  alcohol 
S Para-Nitrobenzoylchloride 
h G-amma-Dipropylaminoethylester  of 
para-nitrobenzoic  acid 
i G-amma-Dipropylaminoethylester  of 
para-aminobenzoic  acid 

IV  SUmiARY 
V BIBLIOGRAPHY 
PART  II 


I REACTION  OF  ACID  CHLORIDES 


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THE  PREPARATION  OF 


G-A]iE'i[A-DIPROPYLA^/.INOETHYLESTSR  OF  PARA-AMINOBENZOIC  ACID 

I INTRODUCTION 

Various  anesthetic  compounds  have  been  prepared  and  the 
work  is  still  being  carried  on  with  the  object,  in  view,  of 
finding  Some  compound  that  will  have  the  anesthetic  properties 
of  cocaine.  Novooalne  (procaine) 

has  met  the  requirements  to  a large  extent  but  it  has  consider- 
able toxic  effect  and  search  is  being  made  for  a compound  that 
is  readily  soluble  and  having  no  toxic  effects.  Novocalne  is 
used  very  extensively  in  modern  surgery  and  has  met  the  re- 
quirements very  well  to  date.  However,  cocaine  has  greater 
penetrating  power  and  consequently  is  widely  used  for  certain 
kinds  of  anesthesia.  If  a compound  could  be  prepared  which 
would  have  the  penetration  power  of  cocaine  with  less  toxicity, 
than  novocalne,  there  would  be  a wide  field  for  its  use,  also 
very  valuable  to  the  medical  profession.  The  group  which  has 
the  desired  effect  is  -c.-o  and  the  best  manner  to 

it  ^ 

attack  this  problem  seems  to  be  to  prepare  a series  of  compounds 
in  which  this  group  is  present,  especially  replacing  the  ethyl 
groups  with  others. 


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II  HISTORICAL  AND  THEORETICAL 


The  first,  methods  to  alleviating  pain,  as  used  by  the  oldest 
Assyrians,  were  to  compress  the  veins  in  the  neck.  The 
Ssyptlans  knew  of  a few  sleep  producing  compounds.  Amoung  the 
first  to  be  used  were  opium  and  Indian  Hemp.  Cocaine  was  studied 
very  extensively  by  Dr.  H.M.Beggs  (2),  who  has  done  a large 
amount  of  research  in  anesthetics.  A search  for  a new  local 
anesthetic  which  would  substitute  cocaine  or  offer  improvements 
over  it  has  been  carried  on  ever  since  the  advent  of  synthetic 
organic  chemistry.  The  structure  of  cocaine  was  studied  and  the 
group  which  had  the  peculiar  anesthetic  properties  determined. 
Now,  the  problem  remains,  to  arrange  compounds  around  this 
group  of  such  structure  and  physiological  action  so  as  to  have 
no  toxic  effect  and  yet  be  readily  soluble. 

Novocaine  has  been  studied  by  many  workers,  with  a viev/  of 
improving  its  physiological  action.  Various  strait  chains 
have  been  substituted  for  the  aniline  group,  in  all  cases  giving 
a compound  inert  physiologically.  The  length  of  the  side  chain 
has  been  varied,  also  the  ester  group  has  been  placed  various 
distances  from  the  ring.  In  fact  most  all  conceivable  compounds 
have  been  manufactured,  some  active,  some  inert. 

V.Peckmann  and  Berkhard  (1)  have  prepared  a compound  by 
adding  four  grams  of  methyl  ester  of  acrylic  acid  to  a cooled 
ethereal  diazo  solution  obtained  from  lOcc  of  nitroso-methyl 
urethan.  Reaction  is  complete  after  one  hour  and  since  it  does 
not  show  any  tendency  to  crystallize,  it  is  allowed  to  be 
oxidized  by  eight  grams  of  bromine.  The  precipitate  obtained 


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is  boiled  with  concentrated  hydrochloric  acid,  washed  with 
dilute  hydrochloric  acid  and  water  and  recrystallized  from  water. 

Ernest  A.Wildman  (3)  prepared  the  gamma-diethylamino propyl 
eater  of  para-toluic  acid.  It  is  colorless  oil  and  readily 
soluble  in  alcohol  and  benzene,  very  slightly  in  water  and  of 
alkaline  reaction  toward  litmus.  Upon  heating  with  hydrochloric 
acid  or  sodium  hydroxide  it  is  decomposed  into  para-toluic  acid 
and  gamma-diethlyamino  propyl  alcohol,  forming  a salt  with 
hydrochloric  acid  readily  soluble  in  water  and  crystalizing 
from  a mixture  of  acetone  and  ether  in  the  form  of  snow-white 
crystals,  the  aqueous  solution  of  which  is  of  anesthetic  action. 

Knorr  (8)  prepared  methyl  pyrazol  by  the  condensation  of 
sodium  formyl  acetone,  hydraz insulphate,  and  sodium  hydroxide, 
in  molecular  proportions.  One  mole  of  sodium  formyl  acetone 
is  dissolved  in  a little  water,  and  to  this  solution  the 
mixture  of  one  mole  powdered  hydrazin  sulphate  and  sodium 
hydroxide  is  added,  and  enough  water  to  keep  all  in  solution. 

This  is  warmed  and  the  methyl  pyrazol  seperates  as  a heavy  oil. 

The  majority  can  be  fractionated  and  the  rest  extracted  with  ether. 

Dr.  O.Kamm  (5)  in  one  of  his  papers  of  a series  on, "The 
Relationship  Between  Chemical  Constitution  and  Physiological 
Action  in  Local  Anesthetics",  gives  a description  of  several 
of  the  compounds  he  has  prepared,  also  a discussion  of  their 
homo logs . 

For  instance,  one  of  the  compounds  he  prepared  was. 


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1 


This  compound  has  three  carbon  atoms  between  the  oxygen  and 
nitrogen  atoms.  The  natural  occuring  anesthetic,  cocaine,  also 
possesses  such  a structure,  , 

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whereas  cocaine  oossesses  a chain  of  three  carbon  atoms  between 


Procaine  contains  the  structure, 


the  nitrogen  and  oxygen  atoms  in  the  amino  alcohol.  Cocaine  is 
considered  more  toxic  than  procaine  but  for  certain  types  of 
anesthetia,  it  showa  stronger  action  than  procaine  because  of 
its  greater  powers  of  penetration. 

This  new  homologue  of  procaine  possesses  the  three  carbon 
atoms  the  same  as  cocaine  and  for  that  reason  one  would  expect 
it  to  have  physiological  action  similiar  to  both  procaine  and 
cocaine.  Tests  show  that  this  is  true,  also  that  this  new  com- 
pound is  more  toxic  than  procaine. 

One  compound  (4)  which  possesses  anesthetic  properties  is 


o 


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CL  ^ d ~ — o — a 

H I'f  ^ 

which  is  very  similiar  in  structure  to  novocaine. 


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This  new  compound  has  greater  anesthetic  properties  than  novocaine. 
It  has  been  found  by  Dr.O.Kamra  that  the  maximum  anesthetic  affect 


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seems  to  occur  when  the  carboxyl  group  is  removed  from  the  ring. 

The  purpose  in  this  experiment  was  to  replace  the  ethyl 
group  by  n~propyl  groups  and  see  if  the  compound  would  have 
greater  anesthetic  properties.  The  toxic  effects  would  be 
greater  but  if  its  effectiveness  for  the  production  of  surface 
anesthesia  is  considerably  greater  than  that  of  its  lower 
homolog,  it  would  more  than  counterbalance  the  effect  of 
slight  increased  toxicity. 

II  EXPERIMENTAL 

The  directions  followed  in  the  preparation  of  this  compound 
are  given  by  Dr.O.Kamm  (6)  for  the  preparation  of  n-butyl  bromide. 
In  the  rpeparation  of  hydrobromic  acid  for  direct  use  in 
connection  with  the  manufacture  of  alkyl  bromides,  a smaller 
PDoportion  of  water  is  liised  than  would  otherwise  be  the  case. 

A mixture  of  400  g.  of  bromine  and  425  g.  of  ice  is  treated  in 
a cooling  mixture  with  sulfur  dioxide  until  the  bromine  is 
reduced.  296  g.  of  n-propyl  alcohol  are  than  added  and 
following  this  there  are  added  in  several  portions  with  shaking 
200  g.  of  cone,  sulfuric  acid.  The  mixture  is  heated  under  a 
reflux  condenser  for  a period  of  four  hours,  during  vdiich  time 
the  formation  of  propyl  bromide  is  carried  to  completion.  The 
product  is  accordingly  removed  from  the  reaction  mixture  by 
direct  distillation.  The  crude  material  after  washing  with 
water  weighs  422  g.,  and  a purification  with  one-half  its  volume 


rfl'isso!*!  (?t  ;'Sfv4<’4v^a'''.S^vv 

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of  cold  cone,  sulfuric  acid  decreases  this  quantity  by  8 g.  The 
product  is  washed  with  sodium  carbonate  solution,  dried  with  a 
small  quantity  of  calcium  chloride,  and  distilled.  The  yield 
of  product  boiling  at  71-73  degrees  is  40S  g. , which  corresponds 
to  86^  of  the  theoretical  amount.  In  a series  of  experiments 
the  yield  varied  from  43  to  88  percent. 

In  organic  preparations  too  large  a quantity  of  drying  agent 
is  used  with  the  resultant  loss  of  some  of  the  material  due  to 
absorption  of  the  drying  agent.  After  a careful  seperation  of 
the  propyl  bromide  from  the  water  it  was  found  that  from  3 to 
8 g.  of  calcium  chloride  were  sufficient  for  the  drying  of  the 
product. 

Para-toluenesulf onamide 

In  the  preparation  of  this  compound  para-toluenesulf ochloride 
was  treated  with  stronger  ammonia  water.  The  reaction  was  very 
rapid  and  considBrable  heat  given  off.  The  flask  should  be 
cooled  at  intervals  when  the  reaction  becomes  too  rapid.  60  g. 
of  para-toluenesulf  ochloride  and  17  S*  ammonia  were  placed 
in  a beaker  and  slightly  heated,  to  start  the  reaction.  After 
the  reaction  had  stopped  the  mixture  was  heated  to  boiling  and 
filtered.  The  filtrate  is  evaporated  to  dryness  on  the  steam 
bath.  The  solid  is  white  in  color  and  melts  a.t  137  degrees. 

On  a series  of  experiments  the  yield  ranged  from  90  to  9^  percent 
of  para-toluenesulf onamide. 


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Para-toluenesulf ondipropylamlde 


Following  the  method  and  general  synthesis  for  the  methyl- 
amide  compound  as  given  in  Friedlaender  (7),  this  compound  was 
manufactured  from  para-toluenesulf onamide  and  n-propyl  bromide. 
171  g.  of  para-toluenesulf onamide  are  heated  with  100  g.  of  a 
40fo  solution  of  sodium  hydroxide  and  one  liter  of  ethyl  alcohol. 
244.5  g.  of  n-propyl  bromide  are  added  and  the  whole  mass  re- 
fluxed on  a steam  bath  at  100  degrees.  After  one  day  the  mixture 
becomes  neutral  and  40  g.  of  a 40^  solution  of  sodium  hydroxide 
are  added.  This  is  refluxed  as  before  until  neutral  and  40  g. 
more  of  sodium  hydroxide  (40^)  are  added.  The  whole  mass  is 
refluxed  at  100  degrees  until  neutral,  which  takes  from  one  to 
two  weeks,  after  the  last  portion  of  sodium  hydroxide  nas  been 
added.  The  solution  is  light  brown  in  color.  After  the  mixture 
is  neutral  to  litmus,  the  alcohol  is  recovered  by  distillation 
and  the  remaining  mass  is  washed  with  500c c of  water.  The  water 
dissolves  the  sodium  bromide  and  the  oil  seperating  from  the 
water  solution  is  para-toluenesulf ondipropylamlde.  This  oil 
is  light  brown  in  color  and  has  some  impurities  present  as 
propyl  alcohol,  water,  etc.  In  order  to  get  it  in  a pure  con- 
dition it  is  necessary  to  distill  and  this  must  be  done  in 
vacuo  as  the  compound  v;ill  decompose  at  high  temperatures. 

The  oil  was  distilled  at  15  nim  pressure  and  i-emperature  ranging 
from  218  to  224  degrees  C.  In  a series  of  experiments  Lhe 
yields  ranged  from  sixty  to  eighty  percent  ot  the  theory. 


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r.v.Tr,; 


Dipropy lamine 

68  g.  of  para-toluenesulf ondipropylamide  are  placed  into  a 

4 

two  liter  flask  and  31*6  g.  of  chlorosulphonic  add  added.  The 
temperature  rises  very  rapidly  and  the  reacting  mixture  should 
he  placed  under  a reflux  condenser  at  once.  Sulfurous  rumes 
come  off  in  considerable  quantity  and  the  reacting  should  oe 
carried  out  in  a hood.  After  the  rirst  reaction  has  ceased, 
a small  flame  is  placed  under  the  flask.  Very  little  neat  is 
necessary  as  the  heat  of  reaction  is  quite  high.  When  the  fumes 
have  stopped  coming  off  and  the  former  liquid  is  a viscous 
black  mass,  the  neat  is  removed  and  the  flask  allowed  to  cool. 
Wlien  cold  there  should  oe  a black  solid  left  in  the  flask. 

Enough  sodium  hydroxide-  is  added  to  the  solid  to  make  it  alkaline 
to  litmus  and  than  steam  distilled.  Tne  condenser  should  be 
fitted  with  an  adapter  which  is  fastened  into  an  erlenmeyer 
flask  with  a cork.  This  erlenmeyer  is  emersed  in  an  ice  oath 
because  dipropylamine  has  a low  coiling  point.  Tne  distillate 
is  made  acid  to  litmus  with  hydrochloric  acid  and  evaporated. 

The  dipropylamine  is  present  as  the  hydrochloride  and  is  a solid. 
This  solid  is  dissolved  in  an  alkaline  solution  and  the  amine 
seperates  as  an  oil  on  the  solution.  It  has  such  a low  boiling 
point  that  it  can  be  distilled  off  in  the  pure  condition.  Di- 
propy lamine  is  a light  yellow  liquid  v/hich  boils  at  66  to  71 

degrees  and  has  a strong  odor  of  ammonia. 


Ethylene  oxide 

50  g.  of  ethylene  chlorhydrate  are  refluxed  with  25  S* 
sodium  hydroxide.  The  ethylene  chlorhydrate  is  placed  in  a 
liter  flask  which  has  a seperatory  funnel  and  reflux  condenser 
attached.  The  sodium  hydroxide,  50^  solution,  is  placed  in  the 
seperatory  funnel,  and  the  reflux  condenser  is  connected  with 
a tube  to  another  condenser  immersed  in  ice.  The  chlorhydrate 
is  heated  to  boiling  and  the  sodium  hydroxide  solution  added 
slowly.  The  water  and  chlorhydrate  are  condensed  in  the 
condenser  and  flow  back  into  the  flask,  whereas  the  ethylene 
oxide,  which  boils  at  ten  degrees,  passes  on  thru  the  tube  into 
the  ice  condenser  where  it  is  liquified.  Below  the  ice  condenser 
the  oxide  compourd  is  collected  in  a tube  v/hich  is  completely 
surrounded  with  ice  and  salt.  IThen  the  tube  is  filled  it  is 
sealed  and  in  that  condition  the  ethylene  oxide  can  be  kept 
indef initely . It  is  colorless  liquid  with  an  odor  similar  to  ether 

Dipropylaminoethyl  alcohol 

30  g.  of  dipropylamine  were  placed  into  a carous  tube  and 
the  whole  placed  in  a tube  of  ice  and  salt.  The  reason  being  to 
cool  the  tube  and  compound  below  zero  so  as  to  add  the 
ethylene  oxide.  The  sealed  tube  of  ethylene  oxide  is  cooled 
below  zero  and  the  top  broken  off.  The  oxide  is  than  introduced 
into  the  carous  tube.  The  top  of  the  tube  is  sealed  with  an 


t»a. 


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oxygen  flame,  the  other  end  being  kept  in  the  ice  and  salt, 
great  care  must  be  taken  to  have  the  glass  heavy  around  the 
whole  seal.  If  the  glass  is  drawn  out  too  much  it  will  not 
stand  the  pressure.  The  tube  is  than  placed  into  a steel  Jacket 
and  the  whole  placed  into  a steam  cone  and  heated  to  about  100 
degrees.  The  reaction  goes  to  completion  in  sixteen  hours.  The 
top  is  broken  off  and  the  liquid  distilled.  The  final  product 
is  a heavy  viscous  liquid,  colorless  and  having  a boiling  point 
of  132  to  188  degrees.  In  the  experiment  carried  out  the  yield 
was  62%  of  theory. 

Para-nitrobenzoylchloride 

The  best  manner  to  manufacture  this  compound  on  a small 
scale  is  by  use  of  phosphorous  pentachloride  and  para-nitro- 
benzoic  acid.  The  final  product  must  be  distilled  and  here  is 
where  caution  must  be  taken  as  the  phosphorous  pentachloride, 
which  has  not  reacted,  will  distill  at  about  the  sa^me  temperature 
as  the  nitro  compound  and  sublime  in  the  tube,  causing  an  ex- 
plosion. 34  g.  of  phosphorous  pentachloride  were  added  to  35  S* 
of  para-nitrobenzoic  acid  and  heated  on  the  steam  bath.  Akter 
the  reaction  has  ceased  the  liquid  is  distilled  under  vacuo. 

The  yield  was  82^  of  theory. 


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G-anima-dipropylaniinoethylester  of  para-nltrobenzoic  acid 

20  g.  of  dlpropylarainoethyl  alcohol  V7ere  placed  in  a liter 
flask  and  26  g.  of  para-nitrobenzoylchloride  added.  The  nitro 
compound  is  powdered  before  addition  and  introduced  slowly  as 
the  reaction  is  exothermic  and  must  be  cooled  at  intervals  in 
ice  water.  After  all  the  nitro  compound  has  been  added  the 
resultant  product  is  refluxed  for  a short  time,  to  insure  complete 
reaction.  The  clear  liquid  turns  dark  brown  in  color  and  is 
very  viscous.  The  yield  was  46  g.  or  99%  of  theory. 

G-amma-dipropylaminoethylester  of  para-aminobenzoic  acid 

There  are  various  reducing  compounds  but  the  one  chosen 
in  this  case  was  iron.  It  being  most  economical  also  best 
fitted  for  this  reaction.  Five  grams  of  gamma-dipropylamino- 
ethylester  of  para-nitrobenzoic  acid  were  placed  in  a beaker  and 
25  g.  of  iron  added.  This  was  stirred  until  well  mixed  and  than 
a little  water  added,  to  make  a thick  paste  v/ith  the  iron,  care 
being  taken  not  to  have  any  liQuid  on  top  of  the  iron.  The 
mixture  was  stirred  until  quite  hot  and  than  a small  piece  of 
ice  introduced.  The  stirring  was  continued  intil  the  mixture 
was  cool  and  than  placed  on  a steam  cone  for  one  hour.  It  was 
than  filtered  while  hot  and  washed  with  water.  The  compound 
was  extracted  from  the  filtrate  by  use  of  ether.  The  ether 
evaporated  and  the  mass  dissolved  in  alcohol.  This  was 
neutralized  by  the  addition  of  hydrochloric  acid  in  adsolute 


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alcohol.  The  solution  was  made  exactly  neutral,  and  this  is 
very  important,  because  if  it  is  acid  or  alkaline  the  product 
is  decomposed.  The  alcohol  was  evaporated  and  the  product 
crystallized  out.  It  is  a light  brown  crystalline  solid. 

The  physiological  action  of  this  compound  was  not  determined 
by  the  author  as  the  time  was  too  short  in  order  to  make  a 
large  enough  quantity.  But  from  the  structure  one  would  predict 
that  it  had  fairly  good  anesthetic  action. 


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SUI'-CvIARY 


I.  A discussion  of  the  work  done  on  anesthetics, 
especially  novocaine,  is  given  and  some  of  the  properties 
of  the  latter  compound. 

II.  Abstracts  are  given  of  the  methods  of  preparing 
gamma-diethylaminopropyl  ester  of  para-toluic  acid,  and 
methyl  pyrazol. 

a. 

III.  Directions  for  the  preparations  of  propyl  bromide 
by  the  use  of  hydrobromic  acid, also  preparation  of  para- 
toluene  sulfonamide,  para-toluenesulf ondipropylamide, 
dipropylamine,  ethylene  oxide,  di propylamine ethyl  alcohol, 
para-nitrobenzoylchloride,  gamma-dipropylaminoethylester 

of  para-nitro benzoic  acid,  and  gamma-dipropylaminoethylester 
of  para-aminobenzoic  acid  is  given. 


V BIBLIOGRAPHY 


1. 

Ibid 

3595 

2. 

Ber. 

11 

41 

3. 

U.S. Patient 

1,193,651 

(1916) 

4. 

Fried laender 

8 

1007 

5. 

Jour.  am.  Chem.  Soc. 

42 

1030 

6. 

Jour.  Am.  Chem.  Soc. 

12 

305 

7. 

Friedlaender 

1 

34 

8. 

Fried laender 

1 

939 

9. 

Friedlaender 

213 

( 1912) 

10 

. Friedlaender 

212 

( 1912) 

1 1 

. Winther 

1 

60 

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REACTION  OF  ACID  CHLORIDES 


There  are  three  ways  of  preparing  this  compound  as  found 
by  the  author.  50  g.(9)  of  sodium  salcylate  are  added  to 
200cc  of  carbonyl  chloride  in  toluene.  This  is  shaken  for 
some  time  and  allowed  to  stand  over  night.  The  toluene  is 
distilled  in  vacuo  and  the  metahydroxybenzoylchloride  is 
dissolved  in  ligroin  or  carbon  bisulfide.  The  solution 
filtered  and  evaporated.  The  oil  remaining  is  the  meta  compound. 

The  second  method  (10)  of  preparation  is,  to  16  parts  of 
sodium  salcylate  there  are  added  25  parts  of  thionyl  chloride, 
sulfur  dioxide  coming  off.  The  temperature  should  not  exceed 
30  degrees.  As  soon  as  the  boiling  ceases  the  reaction  is 
complete  and  the  remaining  thionyl  chloride  is  distilled  off 
in  vacuo.  The  oil  is  dissolved  in  ligroin  and  filtered.  The 
ligroin  is  distilled  under  diminished  pressure  at  lowest  possible 
temperature.  The  oil  remaining  is  the  meta  compound. 

This  last  method  was  used  by  the  author.  (11)  1 10  g.  of 
thionyl  chloride  and  120cc  of  benzene  are  mixed  and  100  g.  of 
sodium  salcylate  are  slowly  added.  The  temperature  of  the 
reacting  mixture  should  be  kept  as  low  as  possible.  The  mass 
will  become  colloidal  in  apperance  and  should  be  placed  in  ice 
for  two  hours.  The  thionyl  chloride  and  benzene  are  distilled 
under  vacuo  and  tha  remaining  solid  dissolved  in  benzene  and 
filtered.  The  filtrate  is  distilled  under  diminished  pressure 
with  the  temperature  as  low  as  possible.  The  remaining  oil  is 
the  meta  compound.  From  several  experiments  the  yield  ranged 


xr'*j!>3fi;0  a'iittT ' .u  n cX  aiji^o^rfe 

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from  80  to  90  percent. 

This  meta  compound  decomposes  upon  standing  and  therefore 
the  paraformaldehyde  was  added  at  once.  To  92  g.  of  meta- 
hydroxy benzoylchloride  there  v;as  slowly  added  35*5  S«  para- 
formaldehyde. The  reaction  mixture  becomes  very  hot  and  has 
considerable  effervescence,  chlorine  being  given  off.  After 
the  reaction  there  was  a white  solid  left.  This  was  tested 
by  qualitative  methods  and  paraformaldehyde  and  the  meta 
compound  were  found  present.  There  is  appa-rently  no  reaction 
between  these  compounds.  The  acid  chlorides  and  aldehydes 
react  with  ease  but  the  phenol  acid  chlorides  will  not  react 
with  the  alaphatic  aldehydes. 


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